BCHM 461 Fall 2005 Biochemistry I

1. BCHM 461Fall 2005Biochemistry I Professor Barbara Gerratana

2. General Information Prof. Barbara Gerratana Office: Room 3506 Biochemistry Bldg e-mail:bgerrata@umd.edu (always welcome). Tel.: 405-1541 (Please restrict telephone inquiries to office hour times). Office hours: Tuesday 4:30-5:30 pm, Thursday 9:30-10:30am Teaching Assistant: Ms. Melissa Resto Office hours: XXXXXXXXX, Room 3510, Biochemistry Bldg, Tel. 405-3949, mresto@umd.edu. Textbooks: Required: 1. Lehninger Principles of Biochemistry, 4th edition, by Nelson and Cox 2. The Absolute, Ultimate Guide to Lehninger Principles of Biochemistry, 4th edition, by Osgood and Ocorr Lehninger Publisher Web Site:http://www.whfreeman.com/lehninger This site provides suggestions for additional readings, interactive tutorials, study aids and links to protein databases. Course Web Site: www.chem.umd.edu/courses.html. This site includes a copy of the syllabus and lectures notes.

3. Course Description The goal of this course is to introduce you to Biochemistry by surveying the various macromolecules that constitute the cell, and direct and facilitate its operation. These macromolecules include proteins, carbohydrates, lipids, and nucleic acids. The focus will be on the chemical properties and three-dimensional structure of these molecules in relationship to their biological function.

4. Grading • Three in–class exams of 75 minutes each. Each of the exams will count for 100 pts and will cover material since the previous exam but will inevitably draw on information from earlier in the semester. • The final exam will be comprehensive and will count for 200 pts. • Your final grade will be based on the total score calculated as the sum of your scores on two out of three in-class exams and on the final exam (maximum 400 points). Grading will be done on a curve based on the overall distribution of the class scores. • Problem sets are optional but highly recommended to prepare you successfully for the exams. • Permission to use calculators will be given depending on the exam. You will be notified the day of the exam if you can use calculator. • Cellular phones should be OFF any time during lectures and exams.

5. Examinations • Examinations will be given the following dates: • Tuesday, September 27 • Tuesday, October 25 • Thursday, November 17 • Final Exam: Tuesday, December 20, 10:30am-12:30pm

6. Cellular Foundation • All organism are based on the same morphological unit, the CELL • Two major classification: eukaryotes (with a membrane enclosed nucleus containing the DNA) and prokaryotes (lacking the nucleus). • What about Viruses? • Viruses are simpler entities than cells and are not classified as living because they lack the metabolic apparatus to reproduce outside the host cells.

7. Domains of Life • Living organisms are divided in three kingdoms or domains • Prokaryotes are divided in :archaebacteria and eubacteria. • Eubacteria include Escherichia coli • Most archeabacteria live in extreme environments. • Phylogenetic relationship are determined by comparing RNA, DNA from different organisms. • Within eubacteria and archaebacteria ther eare two subgroups: -aerobes -anaerobes (obligate anaerobes)

8. Prokaryotic cell • Dimension varies from 1 to 10 M • Common structural feature to bacterial cells: -protective outer membrane (rgid cell wall) -inner plasma membrane that encloses cytoplasm and the nucleoid • Cytoplasm contains: • Ribosomes • proteins • Metabolites • Cofactors • Inorganic ions • Nucleoid contains: a single circular double-stranded DNA molecule Genome sizes in million bp: E. coli 4.6 B. subtilisis 4.2 H. pylori 1.7

9. Prokaryotic cell- Gram Test • Bacteria cell wall are rigid and give the characteristic shape of bacteria cells. • They are medically significant because they are responsible for bacteria virulence. • Bacteria are classified in Gram-positive and Gram-negative according to whether or not they take up Gram stain. • Gram-positive bacteria have thick cell wall surrounding the plasma membrane • Gram-negative bacteria have a thin cell wall covered by a complex outer membrane that allows the exclusion of toxic substances. • Which one do you think are more resistant to antibiotics?

10. Eukaryotic Cell-I • Dimension varies from 5 to 100 M • Characteristics of eukaryotic cell are nucleus and variety of membrane bound organelles with specific function • Genome sizes in million bp: • Homo sapiens 2900 • Mus musculus domesticus 2500 • Saccharomyces cerevisiae 12.

11. Eukaryotic Cell-II

12. Eukaryotic vs. Prokaryotic Cell

13. From the Cell to Macromolecule • Major constituents of cells • Composed of repeating monomeric units that are covalently linked to each other -Amino acids are the monomeric units for proteins -ribonucleotides and deoxyribonucleotides are the monomeric units of RNA and DNA -Not applicable for lipids. Monomeric units are not covalently linked

14. Carbon is the Building Block of Biomolecules • It can form an almost infinite number of compounds as a result of its capacity to make as many as our highly stable bonds. Two carbon atoms can share two electron pairs (double bond) or three (triple bond). • The covalent bond in which carbon participates establishes the stable configuration of the molecule • Only 5 elements (B,C,N, Si and P) have the capacity to make three or more bonds and thus can form chain of covalently linked atoms. All are less stable than carbon. • Of the over 7 million chemical compounds presently known over 90 % are carbon containing substances.

15. Carbon is the Building Block of Biomolecules • Carbon can be tetrahedral, trigonal or linear • C-C single bond have freedom of rotation • Double bonds are shorter and do not allow free rotation

16. Energies of Relevant Covalent Bonds • Hydrogen and oxygen can form only 1 or 2 bonds respectively • N-N bonds are relatively unstable (177 kJ/mol) with respect to C-C • Phoshorus which is below nitrogen in the periodic chart forms even less stable bonds than nitrogen • 1 kcal = 4.184 kJ (C-C bond 83 kcal/mol)

17. Directionality of Biomolecules • There is always a directional sense • Proteins are synthesized from N-terminus to C-terminus • DNA is synthesized from 5’ to 3’ position • Polysaccharides are typically synthesized from 1 to 4 position • The linear sequence of biopolymers can be informational: -in proteins it establishes the final 3D structure -in DNA it establishes the linear sequence of amino acids that will constitute a protein -less important in saccharides -irrelevant for lipids and membranes

18. Functional groups

19. 3D Structure of a molecule • In addition to covalent bonds and functional groups, the stereochemistry of a molecule is central to its function. • Stereochemistry: arrangement of the atoms of a molecule in 3D space • (a) structural formula in perspective form • (b) Ball-and-stick model, showing relative bond lengths and angles • (c) Space-filling model showing atom with the correct van der Waals radius

20. Double Bond Configuration • Configuration is conferred by the presence of either double bonds or chiral centers • Maleic and fumaric acid differ in the arrangement of their substituent groups with respect to double bond. • They are cis-trans isomers. They can not be interconverted without breaking covalent bond, a process that requires energy • Z=cis • E=trans

21. Stereoisomers-I • Chiral molecule are optically active • Achiral molecule are not optically active.

22. Stereoisomers-II • A molecule with one chiral center has two stereoisomers. • A molecule with two or more (n) chiral centers can have 2n stereoisomers. • Enantiomers have nearly identical chemical properties but different physical properties (i.e. interaction with plane polarized light) • Equimolar solution of two enantiomers (a racemic mixture) shows no optical rotation

23. Stereochemical Assignment-I • Priority rule: -OCH2>-OH>-NH2>-COOH>-CHO>CH2OH>-CH3>-H • Group lowest priority pointing away from viewer • Decreased priority clockwise= R • Decreased priority counterclockwise= S

24. Stereochemical Assignment-II • The absolute configuration of simple sugars and amino acids are specified by D, L system or Fisher convention • Fisher projections: horizontal bonds extend above plane and vertical bonds are below plane

25. Molecular Conformation • Molecular conformations represent the spatial arrangement of substituents that are free to assume different positions in space without breaking any bonds.